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Science.com

January 14, 2006



The guiding light — II



By Waqasuddin Khan


TRIBUTE to the greatest medical discoveries continues in this issue of Sci-tech World. These discoveries radically altered medicine and opened previously unknown frontiers.

X-rays
The development of X-ray photography, or radiology, was an enormous leap into the future. For the first time, physicians could see inside the body without opening it up.

With X-rays, surgeons could quickly diagnose fractures, tumours, besides other ailments and plan more intricate operations. As a result, surgery rapidly developed.

Early in 1895, German physicist Wilhelm Roentgen was experimenting with a Crookes tube — a pear-shaped glass tube emptied of air, with electrodes sealed into opposite ends of the tube. When the negative electrode, or cathode, received a high-voltage electrical current, it glowed white-hot and emitted a stream of invisible, electrically charged particles called cathode rays.

These rays moved towards positive electrode, or anode, of the tube. If only a little air remained inside Crookes tube, cathode rays striking the glass at the other end of the tube would produce a yellow-green fluorescence.

Roentgen’s experiments had confirmed that cathode rays could pass through an aluminum-covered window in the wall of a Crookes tube. To discover whether cathode rays could also go through the glass wall of a Crookes tube, he placed a piece of paper coated with a barium salt near the tube’s anode. Such a paper was known to glow when hit with cathode rays.

Roentgen covered the tube with black cardboard to block the tube’s fluorescence and switched his laboratory’s lights off to better see what happened. While testing the tube, Roentgen noticed a strange glow some distance away.

The glow was coming from another piece of coated paper that was about a metre away from the Crookes tube. Repeatedly turning his tube on and off, Roentgen learned that the paper only glowed when the tube was on. The paper still glowed when he moved it even farther away and even when he shielded it, first with a pack of cards and then with a book.

Roentgen knew that cathode rays were not strong enough to cause this distant fluorescence. There could only be one explanation: Crookes tube was producing previously unknown kinds of electromagnetic waves, which he later called X-rays.

Further experiments showed that these X-rays would not go through lead and would go only partly through other metals.

Later, Roentgen X-rayed his own fingers holding a small lead pipe. To his astonishment, the developed pictures revealed not only the shadow of the pipe but also the bones of his fingers.

Roentgen’s preliminary report, titled On a new kind of X-ray, was published only a few days after he submitted it, a record for rapid publication in science. In 1901 Roentgen became the first scientist ever to receive the Nobel prize in physics.

Blood typing
At the dawn of the 20th century, the Austrian physician Karl Landsteiner made the extraordinary discovery that human blood could be grouped into several different types. This discovery made possible the transfer of blood from one human to another — a medical breakthrough that has saved countless lives.

Landsteiner made the brilliant observation that human blood contains what he called ‘isoagglutinins’. These proteins are capable of agglutinating, or clotting, the red blood cells of blood samples containing isoagglutinins different from their own. Thus, he was able to divide blood into three types: A, B, and O. A rare, fourth type (AB) was later discovered.

Landsteiner showed that the sera of two blood samples containing the same isoagglutinins would not clot the red cells of either type. This discovery permitted the development of a system for safe blood transfusions. For this gift to humankind, Landsteiner received the Nobel prize in medicine in 1930.

Tissue culture
In 1907 American biologist Ross Harrison stumbled upon the discovery that living tissues could be cultured or grown outside a living body. Although Harrison could not have known it at the time, his discovery would become one of the most valued techniques in medicine.

Tissue culture has opened up new ways to study the development of genes (the basic units of heredity), embryos, tumours, toxins, and the pathogens that cause numerous diseases. The technique is also used to produce medicines, vaccines, and replacement tissues, as well as to clone animals.

In 1906 Harrison, an expert on embryos, set out to determine whether nerve fibres grow in local tissues of the body or originate in nerve cells of the brain. He decided to study living nerves in the absence of any surrounding tissue.

To do this, he isolated a portion of the hindbrain of a tiny living frog embryo. To keep his specimen alive, he immersed it in fresh frog lymph (diluted blood plasma carried by the lymphatic system) and placed it under a cover slip so that he could examine it with a microscope. The frog lymph quickly clotted, like blood, and Harrison sealed it with wax to prevent evaporation or contamination of the specimen.

Using a microscope, Harrison discovered that the nerve fibre did actually come from the brain, and not the surrounding tissue. Then Harrison noticed something else: the frog’s brain cells were still growing, even though they were no longer in the frog’s body. Harrison reported his result in May 1907. Since then, tissue culture has allowed researchers to learn more about the basic mechanisms of diseases.

Antibiotics
The discovery of antibiotics opened a whole new front in the war against diseases. Armed with antibiotics, scientists have mounted a major assault on cholera, pneumonia, tetanus, tuberculosis, and many other deadly bacterial infections that had previously struck people down relentlessly.

Some of the most important breakthroughs in science occur unexpectedly, and the discovery of penicillin — perhaps the world’s most widely used antibiotic — is one example. British bacteriologist Sir Alexander Fleming is credited with discovering penicillin, although other scientists before him had noticed that the mould penicillium notatum prevented the growth of some types of bacteria.

It all began when Fleming cultivated staphylococci. He opened a petri dish for a few seconds to put the staphylococci inside. Luckily, two floors below his laboratory, another scientist was studying the mould penicillium notatum. Millions of light mould spores floated into the open dish where Fleming was just putting the staphylococci.

Fleming then left for a short vacation, accidentally leaving the petri dish on the laboratory bench, instead of putting it in a warm incubator. And while he was away, the penicillium mould thrived and secreted penicillin, which oozed around the dish, preventing the growth of staphylococci and leaving the mould isolated from small bacterial colonies in the dish.

Fleming, upon his return, immediately realized what had happened, and he conducted other tests to learn what other bacteria this mysterious mould could kill. Fleming believed that the mould substance, which he named penicillin, could be rubbed onto a cut or a scrape to prevent an infection. A few years later, however, Fleming gave up studying the mould.

Resultantly, penicillin was nearly forgotten until the beginning of World War II. Scientists at Oxford University showed that penicillin could prevent bacterial infections in animals and humans, and they devised a technique to mass-produce pure penicillin. They encouraged companies in the US to manufacture penicillin in vast quantities, and the new drug was credited with saving thousands of lives during the war. In 1945 Fleming and two other Oxford scientists, Sir Howard Florey and Ernst B. Chain, received Nobel prize for the discovery.

DNA
Perhaps the greatest medical breakthrough of the 20th century is the discovery of the structure of deoxyribonucleic acid (DNA). Knowledge of DNA’s chemical structure allowed scientists to understand, for the first time, how DNA replicates itself and passes characteristics from one generation to the next.

This monumental discovery has already revolutionized many aspects of medicine, permitting the development of a vast range of genetically engineered drugs, hormones, and other useful substances.

Swiss physician Friedrich Miescher isolated DNA for the first time in 1869, but the function of the chemical, which is found only in the nucleus of cells, was unknown. As the years passed, scientists learned that DNA contained phosphate, a sugar called deoxyribose, and four different compounds called nucleotide bases.

In 1944, Canadian-born Amer- ican physician and bacteriologist Oswald T. Avery and his colleagues showed, in a series of experiments on bacteria, that DNA transmitted genetic information. Prior to Avery’s groundbreaking work, many biochemists believed that proteins were the source of genetic information.

By 1950, two groups of scientists were in hot pursuit of the structure of DNA. One of the groups was at Cavendish Laboratory in Cambridge, Eng-land. The other group, at King’s College, London, consisted of Maurice Wilkins, a physicist, and Raymond Gosling, a graduate student. They were joined in 1951 by Rosalind Franklin, an expert in X-ray crystallography (a technique that uses a tiny beam of X-rays to create images of the structural relationships between atoms and molecules of chemical substances). Photographs of images produced by X-ray crystallography are called X-ray diffraction photographs.

In 1950, Wilkins received a uniquely pure sample of DNA from a Swiss physicist. From this sample, he was able to pick out single DNA fibres with a glass rod. All the three scientists X-rayed these fibres.

However, a misunderstanding caused Franklin to walk out on the project and, before she left, she was ordered to submit all the X-ray diffraction photographs to Wilkins. One of these photographs showed that the DNA molecule had the shape of a double helix, a structure resembling a twisted ladder.

In the meantime, American biologist James Watson attended a meeting in Naples, Italy, in 1950, in which he saw one of Franklin’s X-ray diffraction photographs. Watson immediately thought the molecule might be a double helix. In the fall of 1951, he joined the team of scientists at Cavendish Laboratory, where he convinced a British biophysicist, Francis Crick, that a combination of model building — using plastic balls, wires and steel plates — and X-ray crystallography could lead them to the structure of DNA.

The double helix by itself, however, was not the only secret to the DNA molecule. Its entire chemistry needed to be explained. Watson, unbeknownst to Wilkins, was now convinced that DNA had a helical structure and was working feverishly with Crick on their increasingly complex model of the molecule, which they finished during the second week of 1953. This model incorporated all the known chemical components of DNA and closely matched the diffraction pattern observed in Franklin’s photograph.

Watson and Crick accurately deduced that the two strands of the double helix separated before cellular division, providing templates, or patterns, for the creation of two new DNA molecules, identical to the original.

On April 25, 1953, the journal Nature published one article from the Cambridge laboratory and two from King’s College in London on the molecular structure of DNA. Many felt that the key to life itself had been revealed. Wilkins, Watson, and Crick shared the 1962 Nobel prize in physiology or medicine.

Equipped with a map of the human genome (the complete genetic code), researchers hope to root out the genetic causes of a wide range of inherited diseases, from schizophrenia to cystic fibrosis to hemophilia to many types of cancer. (Concluded)

The writer <waqasnayab@gmail.com> is a student



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